Discovery on Controlling Aggression

For the first time, the stress hormone ghrelin has been linked to aggression control.

Researchers say this new discovery can potentially lead to a medicine that can benefit people experiencing long term disabilities, post-traumatic stress disorder, or anxiety disorders.

Mayo Clinic and University of Minnesota researchers made the discovery while they were researching butyrylcholinesterase (BChE), a common plasma enzyme for a therapy geared towards cocaine addicts.

“The idea behind this treatment is to achieve sustained expression of a natural blood-borne enzyme that has been genetically engineered to destroy cocaine on contact and prevent it from reaching the brain, thereby eliminating its reward value,” says Mayo Clinic pharmacologist Stephen Brimijoin, Ph.D.

“Our encouraging test results in rats and mice showed that a single injection of an optimal gene transfer ‘vector’ will meet this standard, will last for years, and appears to cause zero detectable toxicity or adverse effect,” Dr. Brimijoin adds.

Dr. Brimijoin and Marilyn Carroll, Ph.D., a University of Minnesota pharmacology researcher, are the collaborators who have been focusing on this vector for more than five years. They have been performing every safety test possible and studying the ramifications of this drug. Their initial funding that led to foundational discoveries — and a potential cure for cocaine poisoning — came from the Minnesota Partnership for Biotechnology and Medical Genomics.

In their research, they observed two control mice and two mice that had been injected with this enzyme. The caretakers of the mice were consistently calling, saying they needed to separate the control mice from the injected mice because they were constantly fighting. Mayo associate researcher Yang Gao brought the key observation to the attention of Dr. Brimijoin.

“In pursuing the issue of long term safety we followed treated mice for a lifetime and unexpectedly discovered that the animals which were given the gene transfer lived longer than those who had no treatment at all, and unlike the controls which bit each other, they were extremely friendly toward their cage mates,” says Dr. Brimijoin. “Eventually we were able to explain this happy outcome as a result of our enzyme’s action on a hormone called ghrelin, which regulates hunger and feeding, but also has just been demonstrated (by other scientists) to be deeply involved in stress, anxiety, and fear.”

Dr. Brimijoin hypothesizes that ghrelin will protect humans by blocking the toxicity of cocaine.

“If someone were to take a hit, nothing will happen. It doesn’t create an automatic intensifying craving,” he says. He added that mice injected with the vector didn’t want to consume cocaine, even though it was readily available to them.

The researchers are currently seeking funding, so they can test ghrelin on mice at the standard the FDA requires before they can test this vector on humans. A patent application for the enzyme mutations that affects the stress hormone ghrelin has been submitted.